Innate immunity mediated by dendritic cells/macrophages plays a central rolein the early period in tumor treatment using gene of Mycobacterium tuberculosisantigen

The Journal of Veterinary Medical Science

Yoshiyuki KOYAMA¹  Kikuya SUGIURA²  James K. CHAMBERS²  Shingo HATOYA²  Takahiro USHIGUSA²  Tomoko ITO²  Toshio INABA³  Kazuyuki UCHIDA³  Ryoji KANEGI³  Kenichi WATANABE⁴  Aya HASEGAWA⁴ 

[1] Animal Regerative Medicine Center Hospital, Naka-ku,Yokohama, Kanagawa 231-0033 Japan;Department of Advanced Pathobiology, Graduate School ofLife and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka598-8531 Japan;Department of Veterinary Pathology, Graduate School ofAgricultural and Life Sciences, The University of Tokyo, Bunyo-ku, Tokyo 113-5657,Japan;Japan Anti-tuberculosis Association, Shin-YamanoteHospital, Higashimurayama, Tokyo 189-0021 Japan

关键词: dendritic cells/macrophages;    early secretory antigenic target-6;    gene therapy;    innate immunity;    tumor;   

DOI  :  10.1292/jvms.17-0466

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

By using a complex of DNA, polyethylenimine and chondroitin sulfate, the invivo transfection of early secretory antigenic target-6 (ESAT-6) gene intotumor cells was found to cause significant suppression of the tumor growth. In order toapply the method in clinical cancer treatment in dogs and cats, mechanisms underlying thesuppressive effects were investigated in a tumor-bearing mouse model. The transfectionefficiency was only about 10%, but the transfection of ESAT-6 DNA nevertheless inducedsystemic immune responses against ESAT-6. By triple injection of ESAT-6 DNA at three dayintervals, the tumor was significantly reduced and almost disappeared by 5 days after thestart of treatment, and did not increase for more than 15 days after the final treatment.In the immunohistochemistry, a larger number of dendritic cells (DCs)/macrophagesexpressing ionized calcium-binding adapter molecule 1 and CD3+ T cells wasobserved in tumors treated with ESAT-6 DNA, and their population further increasedsignificantly by day 5. Moreover, the amount of tumor necrosis factor, which is anapoptosis-inducing factor produced mainly by DCs/macrophages, was greater in the ESAT-6DNA treated tumors than in controls, and increased with repeat of the treatment. Theseresults indicate that in vivo transfection of ESAT-6 DNA into tumor cellselicits significant inhibition of tumor growth by inducing potent activity of innateimmunity mediated by DCs/macrophages, which may be followed by adaptive immunity againsttumor associated antigens, elicited by the costimulation with ESAT-6 antigen.

【 授权许可】

Unknown